Ectopic LTαβ directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase

Lymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, and high endothelial venules (HEVs) expressing mucosal addressin cell adhesion molecule (MAdCAM-1) and peripheral node addressin (PNAd), ligands for naive cell entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LTalphabeta's activities in lymphoid organogenesis, mice simultaneously expressing LTalpha and LTbeta under rat insulin promoter II (RIP) control were compared with RIPLTalpha mice in a model of lymphoid neogenesis and with LTbeta(-/-) mice. RIPLTalphabeta pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLTalpha pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin(+) cells were more frequent. In contrast to the predominant abluminal PNAd pattern of HEV in LTbeta(-/-) MLN and RIPLTalpha pancreatic infiltrates, PNAd was expressed at the luminal and abluminal aspects of HEV in wild-type LN and in RIPLTalphabeta pancreata, coincident with HEC-6ST. These data highlight distinct roles of LTalpha and LTalphabeta in lymphoid organogenesis supporting the notion that HEC-6ST-dependent luminal PNAd is under regulation by LTalphabeta.